Phosphodiesterase 5 inhibition protects against increased intra-abdominal pressure-induced renal dysfunction in experimental congestive heart failure

Abstract

Aims: Congestive heart failure (CHF) is associated with impaired renal function. Previously, we have demonstrated that rats with decompensated CHF exhibited exaggerated sensitivity to the adverse renal effects of increased increased intra-abdominal pressure (IAP) as compared with normal controls. This study tested whether phosphodiesterase 5 (PDE5) inhibition protects against the adverse renal effects of increased IAP in rats with CHF.

Methods and results: Following baseline periods, rats with compensated and decompensated CHF induced by the placement of an aorto-caval fistula (ACF), rats with myocardial infarction (MI) induced by left anterior descending (LAD) artery ligation, and sham controls were subjected to consecutive IAPs: 7, 10, or 14 mmHg. Urine flow (V), Na(+) excretion (U(Na)V), glomerular filtration rate (GFR), and renal plasma flow (RPF) were determined. The effects of pre-treatment with tadalafil on the adverse renal effects of IAP were examined in rats with decompensated CHF and MI. Elevation of IAP to 10 and 14 mmHg produced linear reductions in these parameters. Basal renal function and haemodynamics were lower in CHF rats. Decompensated CHF rats and MI rats that were subjected to 10 and 14 mmHg exhibited exaggerated declines in V, U(Na)V, GFR, and RPF. In contrast, no adverse renal effects were observed in rats with compensated CHF subjected to IAP. Pre-treatment of decompensated CHF rats and MI rats with tadalafil ameliorated the adverse renal effects of high IAP.

Conclusion: Decompensated CHF and MI rats are vulnerable to the adverse renal effects of IAP. Tadalafil abolishes IAP-induced renal dysfunction, supporting a therapeutic role for PDE5 inhibition in CHF associated with ascites.